Exploratory Study of EBV-TCR-T Cell Injection for EBV DNAemia After Allogeneic Hematopoietic Stem Cell Transplantation

An Exploratory Clinical Study of EBV-TCR-T Cell Injection for the Treatment of EBV DNAemia After Allogeneic Hematopoietic Stem Cell Transplantation

Epstein-Barr virus (EBV) DNAemia is a common and potentially serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may progress to EBV-associated lymphoproliferative disorders. Current treatment options are limited, and effective immune-based therapies are still needed.

This is an investigator-initiated, exploratory, open-label, single-arm clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of EBV-specific T cell receptor-engineered T cells (EBV-TCR-T cell injection) in patients with EBV DNAemia after allo-HSCT. Eligible participants will receive intravenous infusions of EBV-TCR-T cells at escalating dose levels. Safety outcomes, EBV-DNA clearance, and preliminary efficacy will be assessed, along with pharmacokinetic and pharmacodynamic characteristics of the infused cells.

This study is an investigator-initiated, exploratory, open-label, single-arm, dose-escalation clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of EBV-specific T cell receptor-engineered T cell injection (EBV-TCR-T) in patients with EBV DNAemia following allogeneic hematopoietic stem cell transplantation.

EBV-TCR-T cells are genetically engineered T lymphocytes expressing EBV antigen-specific T cell receptors, enabling targeted recognition and elimination of EBV-infected cells. In this study, peripheral blood mononuclear cells will be collected from the patient or an appropriate donor and used to manufacture EBV-TCR-T cells, which will be administered by intravenous infusion.

The study will enroll approximately 4 to 18 participants. Three dose levels are planned: 1×10^5 cells/kg, 5×10^5 cells/kg, and 1×10^6 cells/kg per infusion. Participants will receive weekly infusions, with up to three infusions administered at Day 0, Day 7, and Day 14, depending on safety and virologic response. Dose escalation will follow a predefined dose-limiting toxicity (DLT)-based design to determine the maximum tolerated dose and the potential optimal biologic dose.

The primary objectives of the study are to evaluate safety and tolerability, including the incidence and severity of adverse events, immune-related adverse events, serious adverse events, and dose-limiting toxicities. Secondary objectives include assessment of preliminary efficacy, such as EBV-DNA clearance rate, time to EBV-DNA negativity, and changes in EBV viral load. Pharmacokinetic and pharmacodynamic analyses will assess in vivo expansion, persistence of EBV-TCR-T cells, and associated immune biomarkers.

Participants will be followed for safety, efficacy, and immune response for up to 12 months after the first infusion, with long-term safety follow-up conducted according to protocol requirements.

Inclusion Criteria:

• Age ≥ 18 years at the time of enrollment.
• History of allogeneic hematopoietic stem cell transplantation.
• Presence of Epstein-Barr virus (EBV) DNAemia confirmed by quantitative polymerase chain reaction (qPCR) in peripheral blood.
• EBV DNAemia persisting or increasing despite standard management, as determined by the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate organ function as defined by the study protocol.
• Ability to understand and willingness to sign written informed consent.

Exclusion Criteria:

• Diagnosis of EBV-associated lymphoproliferative disorder requiring immediate cytotoxic chemotherapy.
• Active, uncontrolled infection other than EBV.
• History of severe autoimmune disease requiring systemic immunosuppressive therapy.
• Uncontrolled graft-versus-host disease requiring high-dose systemic corticosteroids or other immunosuppressive treatment.
• Prior treatment with EBV-specific adoptive T cell therapy within a defined washout period.
• Known active malignancy other than EBV-related disease that may interfere with study participation.
• Pregnant or breastfeeding women.
• Any medical, psychological, or social condition that, in the opinion of the investigator, would interfere with safe participation in the study.